9 Preconception Vulnerability

Overview

Reproductive vulnerability to heat does not begin at implantation—it can be traced to the preconception period, including folliculogenesis, ovulation, and early embryonic development. Heat stress during these stages may impair fertility, affect hormone balance, and damage oocytes or early embryos.

Effects on Folliculogenesis and Ovulation

Folliculogenesis, the process by which ovarian follicles mature, is temperature-sensitive. In animal models:

• Heat exposure reduces granulosa cell function, aromatase activity, and estrogen production

• Estradiol suppression is associated with smaller or less viable follicles

• Progesterone secretion may also be impaired following heat exposure

In dairy cows, heat stress suppressed aromatase activity in granulosa cells and decreased estradiol in follicular fluid and plasma (Badinga et al., 1993).

In goats, heat stress during the follicular recruitment phase reduced follicle size, delayed luteinising hormone (LH) surges, and decreased estradiol output (Ozawa et al., 2005).

Ovulatory Disruption

Ovulation depends on a precise hormonal cascade involving an LH surge. Heat stress can:

• Delay or reduce LH secretion

• Alter timing and effectiveness of ovulation

• Reduce ovulation rate in species with multiple ova release

Alliston and Ulberg (1961) showed that heat exposure in sheep reduced the number of ova released per cycle, even when estrous behavior was unchanged.

In human populations, high environmental temperature has been associated with reduced conception rates in the weeks following heatwaves (Barreca et al., 2018; Heutel et al., 2021).

Preimplantation and Early Embryonic Risk

After fertilisation, the embryo enters a critical window of rapid cell division, gene activation, and migration. This preimplantation period is highly heat-sensitive.

Key findings from animal studies:

• Mouse and bovine embryos exposed to 41°C for just 12 hours at the 2-cell stage failed to progress to the 4-cell stage (Edwards et al., 1997)

• Embryos exposed to heat at the 8–16 cell stage showed increased apoptosis and reduced cell number, but were able to develop thermotolerance if preconditioned with mild heat (Paula-Lopes & Hansen, 2002)

• Heat stress disrupts expression of HSP70, BAX, and aromatase, increasing oxidative stress and compromising viability (Li et al., 2016)

Heat Stress as a Teratogen

Heat is classified as a teratogen, meaning it can cause birth defects. Unlike chemical teratogens, the harmful effects of heat were first demonstrated in animals, then confirmed in humans.

Mechanisms include:

• Apoptosis of proliferating cells

• Disruption of cell migration

• Damage to placental development

• Reduced uterine blood flow

Exposure to elevated maternal temperature (≥39°C) during the first trimester is associated with neural tube defects and craniofacial abnormalities in humans (Edwards, 1995; Shiota & Opitz, 1982).

Timing Matters

The timing of heat exposure is critical:

• Follicular phase and ovulation: hormonal signaling and oocyte maturation are vulnerable

• Fertilisation to implantation: heat can impair cleavage, reduce blastocyst formation, and increase resorption

• Implantation window: hyperthermia may disrupt uterine receptivity and trophoblast invasion

In embryo transfer studies, pregnancy rates dropped from 56.5% to 9.5% when heat-stressed embryos were transferred into non-stressed ewes (Alliston & Ulberg, 1961)

Recap

• The preconception period is a window of sensitivity for both the oocyte and early embryo

• Heat stress disrupts hormone production, follicle maturation, and early embryonic development

• Even before pregnancy is confirmed, ambient temperature can affect outcomes through teratogenic and endocrine-mediated pathways

References

• Alliston, C. W., & Ulberg, L. C. (1961). Successful fertilization and early embryo development in sheep under elevated temperature conditions. Journal of Animal Science, 20(3), 608–612.

• Badinga, L., Thatcher, W. W., Diaz, T., Drost, M., & Wolfenson, D. (1993). Effect of environmental heat stress on follicular development in lactating dairy cows. Theriogenology, 39(2), 797–810.

• Barreca, A. I., Deschênes, O., Guldi, M., & Mansur, E. T. (2018). Maybe next month? Temperature shocks, climate change, and dynamic adjustments in birth rates. Journal of Labor Economics, 36(S1), S93–S126.

• Edwards, M. J. (1995). Hyperthermia and birth defects. Reproductive Toxicology, 9(5), 411–425.

• Li, R., et al. (2016). Heat stress damages granulosa cell viability and steroidogenesis. Cell and Tissue Research, 365(2), 379–389.

• Ozawa, M., et al. (2005). Effects of acute heat stress on the estrous cycle, follicular development and steroidogenesis in goats. Animal Reproduction Science, 85(1-2), 83–93.

• Paula-Lopes, F. F., & Hansen, P. J. (2002). Apoptosis in bovine preimplantation embryos exposed to heat shock. Biology of Reproduction, 66(6), 1749–1757.

• Shiota, K., & Opitz, J. M. (1982). Neural tube defects and maternal hyperthermia in early pregnancy: epidemiology in a human population. American Journal of Medical Genetics, 12(3), 281–288.